Management of Exogenous Cushing Syndrome from Chronic Dexamethasone Use
Immediate Action: Stop Dexamethasone and Begin Gradual Taper
The primary management is to immediately discontinue the causative dexamethasone and initiate a gradual taper to physiologic glucocorticoid replacement, as abrupt cessation will precipitate life-threatening adrenal crisis due to suppressed HPA axis. 1, 2
- Exogenous steroid cessation is the most direct and effective intervention for exogenous Cushing syndrome 1
- The HPA axis is suppressed after chronic supraphysiologic glucocorticoid exposure, requiring replacement therapy during recovery 2, 3
- Drug-induced secondary adrenocortical insufficiency may persist for months after discontinuation, necessitating stress-dose coverage during intercurrent illness 4
Tapering Strategy and Transition to Physiologic Replacement
Initial Taper Phase (Days 1-7)
- Reduce dexamethasone by approximately 25-50% every 2-3 days while monitoring for adrenal insufficiency symptoms (fatigue, nausea, hypotension, hypoglycemia) 1, 4
- Morning cortisol <3 mcg/dL indicates adrenal insufficiency; >15 mcg/dL suggests HPA axis recovery 1
- Transition to hydrocortisone when dexamethasone reaches approximately 1-2 mg daily, as hydrocortisone better recreates diurnal cortisol rhythm 1, 5
Physiologic Glucocorticoid Replacement
- Initiate hydrocortisone 15-20 mg daily in divided doses (10 mg upon waking + 5 mg early afternoon, or 10 mg + 5 mg + 2.5 mg if three doses needed) 6, 1, 5
- The first dose must be taken immediately upon waking, and the last dose at least 6 hours before bedtime to avoid sleep disturbances 5
- Maximum dose is 30 mg daily for residual symptoms; titrate to lowest effective dose 1, 5
- Mineralocorticoid replacement (fludrocortisone 50-100 mcg daily) is typically NOT required in secondary adrenal insufficiency from exogenous steroids, but assess if postural hypotension or hyponatremia develops 6, 5
Philippine-Compliant Prescription for Physiologic Replacement
Rx:
Generic Name: Hydrocortisone
Strength: 10 mg tablets
Form: Oral tablet
Dose: 10 mg in the morning (upon waking) + 5 mg in early afternoon (around 1-2 PM)
Route: Oral
Frequency: Twice daily
Quantity: #90 tablets (30-day supply)
Instructions: Take 10 mg (1 tablet) immediately upon waking. Take 5 mg (½ tablet) in early afternoon (1-2 PM), at least 6 hours before bedtime. Do NOT skip doses. Double or triple dose during fever or illness. Seek emergency care if vomiting prevents oral intake.
Refills: 2 refills with mandatory follow-up every 4 weeks initially, then every 3 months after stabilization
Follow-up: Return in 2 weeks for morning cortisol, electrolytes, glucose, blood pressure check. Monthly visits for first 3 months, then quarterly.
Monitoring: Morning (8 AM) cortisol every 2-4 weeks initially; serum sodium, potassium, glucose monthly; blood pressure at each visit; weight and symptoms assessment; consider ACTH stimulation test if morning cortisol indeterminate (3-15 mcg/dL) 1, 5
Patient Counseling on Steroid Risks and Complications
Sick-Day Rules (Stress Dosing)
- During minor illness with fever: Double or triple the usual hydrocortisone dose (30-60 mg daily in divided doses) 6, 5
- During vomiting/diarrhea preventing oral intake: Seek emergency care immediately for IV hydrocortisone 100 mg bolus 6, 5
- Major surgery: Requires 100 mg hydrocortisone IM before anesthesia, then 100 mg IM every 6 hours until oral intake resumes 5
- Minor surgery/procedures: 100 mg hydrocortisone IM before procedure, then double oral dose for 24 hours 5
Medical Alert Identification
- All patients MUST wear medical alert bracelet or necklace stating "Adrenal Insufficiency - Requires Hydrocortisone" 6, 5
- Carry emergency card with diagnosis, current dose, and emergency contact information 6
Infection Precautions
- Avoid exposure to individuals with active infections, particularly respiratory and gastrointestinal illnesses 6
- Seek medical attention promptly for any fever, as infection is the most common precipitant of adrenal crisis 6, 5
- Increase hydrocortisone dose at first sign of infection (fever, significant illness) 5
Vaccination Guidance
- Prioritize inactivated vaccines: Influenza (inactivated), pneumococcal (PPSV23 and PCV13), COVID-19, hepatitis B, tetanus-diphtheria-pertussis 5
- Avoid live vaccines while on supraphysiologic doses (>20 mg hydrocortisone daily equivalent): MMR, varicella, zoster (live), yellow fever, oral typhoid 4
- Once on physiologic replacement (15-20 mg hydrocortisone daily), live vaccines may be considered after consultation with endocrinology 5
Skin and Wound Care
- Monitor for easy bruising, thin skin, and poor wound healing—these are signs of excessive glucocorticoid exposure requiring dose reduction 1
- Protect skin from trauma; use gentle skin care products 1
- Report any non-healing wounds or new skin infections immediately 5
Bone Health
- Initiate calcium 1200-1500 mg daily + vitamin D 800-1000 IU daily for all patients on chronic glucocorticoid therapy 5
- Encourage weight-bearing exercise (walking, resistance training) 30 minutes daily to prevent osteoporosis 5
- Consider baseline DEXA scan if glucocorticoid exposure >3 months at supraphysiologic doses 5
Emergency Injectable Glucocorticoid Kit
- Prescribe emergency injectable hydrocortisone 100 mg IM kit (Solu-Cortef Act-O-Vial or equivalent) 6, 5
- Train patient and family members on self-administration technique for use during vomiting, severe illness, or inability to take oral medication 6
- Instruct to inject 100 mg IM and proceed immediately to emergency department 6
Monitoring Parameters and Follow-Up Schedule
Initial Phase (First 3 Months)
- Week 2: Morning (8 AM) cortisol, ACTH, electrolytes (sodium, potassium), glucose, blood pressure, weight 1, 5
- Monthly: Clinical symptoms (energy, appetite, weight), blood pressure (including postural measurements), electrolytes, glucose 6, 5
- Assess for signs of under-replacement: weight loss, fatigue, postural hypotension, salt craving 5
- Assess for signs of over-replacement: weight gain, hypertension, edema, hyperglycemia 5
Maintenance Phase (After 3 Months)
- Every 3 months: Clinical assessment, blood pressure, weight, electrolytes, glucose, HbA1c 5
- Annually: Morning cortisol to assess HPA axis recovery, complete blood count, lipid panel, DEXA scan if indicated 5
- Screen for associated autoimmune conditions (thyroid function tests, vitamin B12) annually 5
Common Pitfalls and How to Avoid Them
- Tapering too quickly: Gradual reduction over weeks to months is essential; abrupt cessation causes adrenal crisis 4, 2
- Inadequate stress-dose education: Failure to increase glucocorticoid dose during illness is the leading cause of preventable adrenal crisis 6, 5
- Overlooking drug interactions: CYP3A4 inducers (phenytoin, phenobarbital, rifampin) increase hydrocortisone clearance, requiring dose adjustment 7, 5
- Ignoring mineralocorticoid needs: While uncommon in secondary adrenal insufficiency, assess for postural hypotension and hyponatremia that may require fludrocortisone 6, 5
- Delaying treatment during suspected adrenal crisis: Administer hydrocortisone 100 mg IV immediately without waiting for diagnostic confirmation 6
When Antagonist Therapy Would Be Appropriate (Not Applicable Here)
- Steroidogenesis inhibitors (ketoconazole, metyrapone, osilodrostat) and glucocorticoid receptor blockers (mifepristone) are second-line therapies for endogenous Cushing syndrome when surgical resection fails or is not feasible 8, 9
- These agents block cortisol synthesis or action at the receptor level, used in pituitary Cushing disease, ectopic ACTH syndrome, or adrenal tumors 8, 9
- In exogenous Cushing syndrome, antagonist therapy is contraindicated and unnecessary because simply stopping the exogenous glucocorticoid source resolves hypercortisolism; adding antagonists would worsen adrenal suppression and precipitate crisis 1, 2
- The pathophysiology differs fundamentally: endogenous Cushing has autonomous cortisol overproduction requiring blockade, whereas exogenous Cushing has suppressed endogenous production requiring replacement 1, 8